Extra-Corporeal Carbon Dioxide Removal in Exacerbations of Chronic Obstructive Pulmonary Disease

Treatment of Acute Exacerbation of Chronic Obstructive Pulmonary Disease With Extracorporeal Carbon Dioxide Removal Associated With High Flow Nasal Cannula Oxygen Therapy. Pilot Study.

Around 20% of the patients requiring hospitalization for Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD) develop hypercapnia, which is associated with an increased risk of death. Once Non Invasive Ventilation (NIV) has been initiated, a reduction in Respiratory Rate (RR) and improvement in pH within 4 h predicts NIV success. If pH <7.25 and RR >35 breath per minutes persist, NIV failure is likely. Worsening acidosis, after initial improvement with NIV, is also associated with a worse prognosis. In addition, it has been shown that delaying intubation in patients at high risk for NIV failure has a negative impact on patient survival. Hence, assessing the risk of NIV failure is extremely important. NIV has some limitations: a) intolerance, discomfort and claustrophobia requiring frequent interruptions; b) poor patient-ventilator synchrony, especially in presence of air leaks or high ventilatory requirements. Since removing carbon dioxide by means of an artificial lung reduces the minute ventilation required to maintain an acceptable arterial partial pressure of carbon dioxide (PaCO2), the investigators hypothesize that applying Extra-Corporeal CO2 Removal (ECCO2R) in high-risk AECOPD patients may reduce the incidence of NIV failure and improve patient-ventilator interaction. After the beginning of ECCO2R, NIV could be gradually replaced by High Flow Nasal Cannula Oxygen Therapy (HFNCOT), potentially reducing the risk of ventilator induced lung injury, improving patient's comfort and probably allowing the adoption of a more physiologically "noisy" pattern of spontaneous breathing.

Study Overview

• Status: Unknown
• Conditions: Respiratory Failure With Hypercapnia
• Intervention / Treatment: Procedure: HFNCOT+ECCO2R

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Milan, Italy, 20122
    • Recruiting
    • Ospedale Maggiore Policlinico

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Patients admitted to Emergency or Pulmonology Department, with history of COPD (pulmonary function test available, any Global Obstructive Lung Disease -GOLD- stage), treated with NIV for acute hypercapnic respiratory failure due to AECOPD defined by:

• pH <7.35 + PaCO2 >45 mmHg (acute hypercapnic respiratory failure) or pH <7.35 + PaCO2 > 20% of baseline value (acute on chronic hypercapnic respiratory failure)
• Acute worsening of respiratory symptoms that results in additional therapy
• Respiratory failure not fully explainable with cardiac failure and at high risk for NIV failure, defined by:
• No improvement or worsening of respiratory acidosis (pH <7.35 and PaCO2 >45 mmHg) after 2 hours of NIV + one of the following: RR ≥30 bpm; use of accessory respiratory muscle or paradoxical breathing (Combination criteria for NIV failure) or
• Glasgow Coma Scale ≤ 11 after 2 hours of NIV (Single criteria for NIV failure) or
• Inability to fit mask (facial deformity/intervention/burns) or marked intolerance to interface because of patient's agitation (Single Criteria for NIV failure)

Exclusion Criteria:

• Age >80 years old
• Contraindications to anticoagulation (any of the following: platelet count <30.000/mm3; activated partial thromboplastin time (aPTT) >1,5; stroke or severe head trauma or intracranial arteriovenous malformation or cerebral aneurysm in the previous 3 months; central nervous system mass lesion; history of congenital bleeding diatheses; gastro-intestinal bleeding in the previous 6 weeks; gastro-esophageal varices)
• Cirrhosis
• PaO2/FiO2 ≤ 150 mmHg
• Hemodynamic instability (80-90 mmHg increase or 30-40 mmHg decrease systolic arterial pressure compared to baseline value or need of vasopressors to maintain systolic blood pressure higher than 85 mmHg or electrocardiogram evidence of ischemia/arrhythmias)
• Body Mass Index ≥37
• Impending respiratory arrest
• Catheter access to femoral vein or jugular vein impossible
• Patient moribund, decision to limit therapeutic interventions
• Opposition to participate obtained from the patient or their legally acceptable representative

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: HFNCOT+ECCO2R; Patients on NIV+ECCO2R who have reached at least for 4 consecutive hours, a RR <25 bpm + pH >7.35 + absence of clinical signs of respiratory distress after treatment with NIV+ECCO2R	Procedure: HFNCOT+ECCO2R; NIV will be discontinued, the ECCO2R setting will be unchanged (both sweep gas flow and blood flow through the artificial lung) and HFNCOT will be started, titrating the fraction of inspired Oxygen (FiO2) to obtain an oxygen saturation at periphery (SpO2) 88-92%; HFNCOT start temperature will be 31°C, the initial flow rate will be 60 L/min.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of partecipants failing HFNCOT+ECCO2R treatment with need of restoring NIV or need of invasive mechanical ventilation	ECCO2R+HFNCOT failure criteria are defined by at least two of the following after at least 1 hour of treatment; Respiratory acidosis (pH <7.35); RR ≥ 30 bpm; Development of progressive hypoxemia (PaO2/FiO2 < 150); Paradoxical breathing	Through study completion, an average of 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of partecipants failing NIV+ECCO2R treatment with need of invasive mechanical ventilation	NIV+ECCO2R failure is defined by two of the following occurring for at least 2 hours: No improvement or worsening of respiratory acidosis (pH <7.35); RR ≥30 bpm; Development of progressive hypoxemia (PaO2/FiO2 ≤150)	Through study completion, an average of 2 years
Number of patients treated with ECCO2R reporting one or more side effects due to ECCO2R	Bleeding (any bleeding event requiring the administration of 1 U of packed red cells); Vein perforation at cannula insertion; Hemodynamic instability (80-90 mmHg increase or 30-40 mmHg decrease systolic arterial pressure compared to baseline value or need of vasopressors to maintain systolic blood pressure higher than 85 mmHg or electrocardiogram evidence of ischemia/arrhythmias); Pneumothorax; Ischemic bowel; Acute kidney failure; Neurological complications (occurrence, after initiation of ECCO2R, of ischemic/hemorrhagic ictus or clinical seizure or cerebral oedema); Metabolic complications (occurrence, after initiation of ECCO2R of hyperbilirubinemia or glucose≥240 mg/dL); Thromboembolic complications (occurrence, after initiation of ECCO2R, of deep venous thrombosis, pulmonary embolism)	Through study completion, an average of 2 years
Variation of pulmonary arterial pressure before and after ECCO2R treatment either in association with NIV or HNFCOT	Echocardiographic measurement	Through study completion, an average of 2 years
Variation of tricuspid annluar plane systolic excursion before and after ECCO2R treatment either in association with NIV or HNFCOT	Echocardiographic measurement	Through study completion, an average of 2 years
Variation of respiratory mechanic during ECCO2R+NIV	Measurement of Respiratory Rate (breaths per minute)	Through study completion, an average of 2 years
Variation of dyspnea during ECCO2R+NIV	Measurement of dyspnea through Borg dyspnea scale. (ranging from a minimum of 0 point, indicating no shortness of breath, to a maximum of 10 points, indicating maximum shortness of breath)	Through study completion, an average of 2 years
Variation of comfort during ECCO2R+NIV	Measurement of comfort through Visual Analogic Scale for comfort, ranging from a minimum of 0 point, indicating no comfort, to a maximun of 10 point, indicating maximum comfort	Through study completion, an average of 2 years
Variation of respiratory mechanic during ECCO2R+HFNCOT	Measurement of Respiratory Rate (breaths per minute)	Through study completion, an average of 2 years
Variation of dyspnea during ECCO2R+HFNCOT	Measurement of dyspnea through Borg dyspnea scale, ranging from a minimum of 0 point, indicating no shortness of breath, to a maximum of 10 points, indicating maximum shortness of breath	Through study completion, an average of 2 years
Variation of comfort during ECCO2R+HFNCOT	Measurement of comfort through Visual Analogic Scale for comfort, ranging from a minimum of 0 point, indicating no comfort, to a maximun of 10 point, indicating maximum comfort	Through study completion, an average of 2 years
Variation of breathing pattern during ECCO2R+NIV	Measurement of expiratory tidal volume, expressed in mL	Through study completion, an average of 2 years
Variation of breathing pattern during ECCO2R+NIV	Measurement of minute ventilation, expressed in liters/minute	Through study completion, an average of 2 years
Variation of acid-base balance during ECCO2R+NIV	emogasanalysis	Through study completion, an average of 2 years
Variation of acid-base balance during ECCO2R+HFNCOT	emogasanalysis	Through study completion, an average of 2 years

Collaborators and Investigators

• Sponsor: Policlinico Hospital
• Collaborators: Niguarda Hospital; San Gerardo Hospital; Ospedale San Paolo
• Investigators: Principal Investigator: Giacomo Grasselli, Professor, Policlinico Hospital

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): July 1, 2019
• Primary Completion (ANTICIPATED): March 1, 2022
• Study Completion (ANTICIPATED): June 1, 2022

Study Registration Dates

• First Submitted: May 27, 2019
• First Submitted That Met QC Criteria: June 15, 2019
• First Posted (ACTUAL): June 18, 2019

Study Record Updates

• Last Update Posted (ACTUAL): June 18, 2019
• Last Update Submitted That Met QC Criteria: June 15, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Signs and Symptoms, Respiratory; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Respiratory Insufficiency; Hypercapnia
• Other Study ID Numbers: Fondazione IRCCS Ca' Granda

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No